Diabetes Medications for Adults With Type 2 Diabetes: An Update

1215 Pages·2016·13.45 MB·English

Comparative Effectiveness Review
Number 173
Diabetes Medications
for Adults With Type 2
Diabetes: An Update
Comparative Effectiveness Review
Number 173
Diabetes Medications for Adults With Type 2 Diabetes:
An Update
Prepared for:
Agency for Healthcare Research and Quality
U.S. Department of Health and Human Services
5600 Fishers Lane
Rockville, MD 20857
www.ahrq.gov
Contract No. 290-2012-00007-I
Prepared by:
Johns Hopkins University Evidence-based Practice Center
Baltimore, MD
Investigators:
Shari Bolen, M.D., M.P.H.
Eva Tseng, M.D., M.P.H.
Susan Hutfless, Ph.D.
Jodi B. Segal, M.D., M.P.H.
Catalina Suarez-Cuervo, M.D.
Zackary Berger, M.D., Ph.D.
Lisa M. Wilson, Sc.M.
Yue Chu, M.S.P.H.
Emmanuel Iyoha, M.B.Ch.B., M.P.H.
Nisa M. Maruthur, M.D., M.H.S.
AHRQ Publication No. 16-EHC013-EF
April 2016
Addendum and Errata
Introduction
During report dissemination in a peer-reviewed journal, Annals of Internal Medicine
requested an update of our search and evidence.
Methods
Search Strategy
We updated the MEDLINE search to identify randomized controlled trials indexed through
December 31, 2015.
Evidence Grading
We updated the evidence from the final Agency for Healthcare Research and Quality report
with results from newly identified randomized trials if these results increased the strength of
evidence from low or moderate to moderate or high.
Results
From the updated MEDLINE search, we identified eight new studies (published in nine
articles)1-9 which met our inclusion criteria, plus six additional publications that were either
extensions or additional analyses of included studies.10-15 Of these, four studies contributed
results which increased the strength of evidence to moderate or high strength; the results of these
studies were incorporated in the publication (Appendix Figure 1).16 The updated strength of
evidence is shown in Table 1. We report four new findings: (1) sulfonylureas had greater
reductions in hemoglobin A1c than dipeptidyl peptidase-4 (DPP-4) inhibitors; (2) sulfonylureas
had less beneficial effects on weight than DPP-4 inhibitors; (3) metformin plus glucagon-like
peptide-1 receptor agonists had greater weight reductions than metformin plus premixed insulins;
and (4) metformin plus thiazolidinediones had less diarrhea than metformin alone (Figures 1 and
4; Appendix Table 6 in the Annals of Internal Medicine manuscript16).
Conclusions
These four new findings strengthen the overall conclusions from the main report.17
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Table 1. Strength of evidence domains for the comparisons and outcomes that changed with the updated search
Comparison Outcome Number of Study Consistency Directness Precision Reporting Strength of Summary
Studies Limitations Bias Evidence
(Subjects)
SU vs. DPP-4 HbA1c 4 (1659) Medium Consistent Direct Precise Undetected Moderate SU favored; pooled
inhibitors mean between-group
difference, -0.2% (95%
CI, -0.3 to -0.1%)
SU vs. DPP-4 Weight 4 (1659) Low Consistent Direct Precise Undetected Moderate DPP-4 inhibitors
inhibitors favored; range in
between-group
differences of 0.7 to 1.8
kg
Metformin + Weight 2 (426) Medium Consistent Direct Precise Undetected Moderate Metformin + GLP-1
GLP-1 receptor receptor agonists
agonists vs. favored; range in
metformin + between-group
premixed insulin differences 1.9 to 5.1
kg
Metformin vs. GI side 11 (4,271) Medium Consistent Direct Imprecise Undetected Moderate Metformin + TZD
metformin + TZD effects 6 studies on for diarrhea; favored for diarrhea;
diarrhea; 1-2 Low for Neither favored for
studies for other GI- other GI-related
other GI-related related outcomes
outcomes outcomes
DPP-4 inhibitors = dipeptidyl-peptidase 4 inhibitors; GI = gastrointestinal; GLP-1 receptor agonists = glucagon-like peptide-1 agonists; GI = gastrointestinal; kg = kilograms; SU =
sulfonylurea; TZD = thiazolidinedione
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References
1. Yang W, Han P, Min KW, et al. Efficacy and safety of dapagliflozin in Asian patients
with type 2 diabetes after metformin failure: A randomized controlled trial. J Diabetes.
2015 Nov 20.
2. Lu Y, Rodriguez LA, Malgerud L, et al. New-onset type 2 diabetes, elevated HbA1c,
anti-diabetic medications, and risk of pancreatic cancer. Br J Cancer. 2015 Dec
1;113(11):1607-14.
3. Tanaka K, Saisho Y, Manesso E, et al. Effects of Liraglutide Monotherapy on Beta Cell
Function and Pancreatic Enzymes Compared with Metformin in Japanese
Overweight/Obese Patients with Type 2 Diabetes Mellitus: A Subpopulation Analysis of
the KIND-LM Randomized Trial. Clin Drug Investig. 2015 Oct;35(10):675-84.
4. Ma Z, Chen R, Liu Y, et al. Effect of liraglutide vs. NPH in combination with metformin
on blood glucose fluctuations assessed using continuous glucose monitoring in patients
with newly diagnosed type 2 diabetes. Int J Clin Pharmacol Ther. 2015 Nov;53(11):933-
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5. Hartley P, Shentu Y, Betz-Schiff P, et al. Efficacy and Tolerability of Sitagliptin
Compared with Glimepiride in Elderly Patients with Type 2 Diabetes Mellitus and
Inadequate Glycemic Control: A Randomized, Double-Blind, Non-Inferiority Trial.
Drugs Aging. 2015 Jun;32(6):469-76.
6. Cai XL, Chen YL, Zhao JJ, et al. Efficacy and safety of avandamet or uptitrated
metformin treatment in patients with type 2 diabetes inadequately controlled with
metformin alone: a multicenter, randomized, controlled trial. Chin Med J (Engl). 2015
May 20;128(10):1279-87.
7. Xiao CC, Ren A, Yang J, et al. Effects of pioglitazone and glipizide on platelet function
in patients with type 2 diabetes. Eur Rev Med Pharmacol Sci. 2015;19(6):963-70.
8. Ross S, Thamer C, Cescutti J, et al. Efficacy and safety of empagliflozin twice daily
versus once daily in patients with type 2 diabetes inadequately controlled on metformin: a
16-week, randomized, placebo-controlled trial. Diabetes Obes Metab. 2015
Jul;17(7):699-702.
9. Tanaka K, Saisho Y, Kawai T, et al. Efficacy and safety of liraglutide monotherapy
compared with metformin in Japanese overweight/obese patients with type 2 diabetes.
Endocr J. 2015;62(5):399-409.
10. Roden M, Merker L, Christiansen AV, et al. Safety, tolerability and effects on
cardiometabolic risk factors of empagliflozin monotherapy in drug-naive patients with
type 2 diabetes: a double-blind extension of a Phase III randomized controlled trial.
Cardiovasc Diabetol. 2015;14(1):154.
11. Chirila C, Zheng Q, Davenport E, et al. Treatment satisfaction in type 2 diabetes patients
taking empagliflozin compared with patients taking glimepiride. Qual Life Res. 2015 Sep
30.
12. Li D, Xu X, Zhang Y, et al. Liraglutide treatment causes upregulation of adiponectin and
downregulation of resistin in Chinese type 2 diabetes. Diabetes Res Clin Pract. 2015
Nov;110(2):224-8.
13. Simo R, Guerci B, Schernthaner G, et al. Long-term changes in cardiovascular risk
markers during administration of exenatide twice daily or glimepiride: results from the
European exenatide study. Cardiovasc Diabetol. 2015;14:116.
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14. Li R, Xu W, Luo S, et al. Effect of exenatide, insulin and pioglitazone on bone
metabolism in patients with newly diagnosed type 2 diabetes. Acta Diabetol. 2015
Dec;52(6):1083-91.
15. Weinstock RS, Guerci B, Umpierrez et al. Safety and efficacy of once-weekly
dulaglutide versus sitagliptin after 2 years in metformin-treated patients with type 2
diabetes (AWARD-5): a randomized, phase III study. Diabetes Obes Metab. 2015
Sep;17(9):849-58.
16. Maruthur NM, Tseng E, Hutfless S, et al. Diabetes Medications as Monotherapy or
Metformin-Based Combination Therapy for Type 2 Diabetes: Systematic Review and
Meta-Analysis. Ann Intern Med. 2016;In press.
17. Bolen S, Tseng E, Hutfless S, et al. Diabetes Medications for Adults with Type 2
Diabetes: An Update. Comparative Effectiveness Review No. 173. (Prepared by the
Johns Hopkins University Evidence-based Practice Center under Contract No. 290-2012-
00007-I.) Rockville, MD: Agency for Healthcare Research and Quality; April 2016.
www.effectivehealthcare.ahrq.gov/reports/final.cfm
Errata
Upon closer review, we found that the primary outcome for Hong 2013 was indeed a
composite cardiovascular outcome, which was not what we had stated and that the followup time
was 5.0 years rather than 3.0 years. We also note that in the Executive Summary we stated that
metformin and GLP-1 receptor agonists were similar for diarrhea, but this was of low and not
moderate or high strength and therefore should have not appeared in that section.
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This report is based on research conducted by the Johns Hopkins University Evidence-based
Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality
(AHRQ), Rockville, MD (Contract No. 290-2012-00007-I). The findings and conclusions in this
document are those of the authors, who are responsible for its contents; the findings and
conclusions do not necessarily represent the views of AHRQ. Therefore, no statement in this
report should be construed as an official position of AHRQ or of the U.S. Department of Health
and Human Services.
None of the investigators have any affiliations or financial involvement that conflicts with
the material presented in this report.
The information in this report is intended to help health care decisionmakers—patients and
clinicians, health system leaders, and policymakers, among others—make well-informed
decisions and thereby improve the quality of health care services. This report is not intended to
be a substitute for the application of clinical judgment. Anyone who makes decisions concerning
the provision of clinical care should consider this report in the same way as any medical
reference and in conjunction with all other pertinent information, i.e., in the context of available
resources and circumstances presented by individual patients.
This report is made available to the public under the terms of a licensing agreement between the
author and the Agency for Healthcare Research and Quality. This report may be used and
reprinted without permission except those copyrighted materials that are clearly noted in the
report. Further reproduction of those copyrighted materials is prohibited without the express
permission of copyright holders.
AHRQ or U.S. Department of Health and Human Services endorsement of any derivative
products that may be developed from this report, such as clinical practice guidelines, other
quality enhancement tools, or reimbursement or coverage policies, may not be stated or implied.
This report may periodically be assessed for the currency of conclusions. If an assessment is
done, the resulting surveillance report describing the methodology and findings will be found on
the Effective Health Care Program Web site at www.effectivehealthcare.ahrq.gov. Search on the
title of the report.
Persons using assistive technology may not be able to fully access information in this report. For
assistance contact [email protected].
Suggested citation: Bolen S, Tseng E, Hutfless S, Segal JB, Suarez-Cuervo C, Berger Z, Wilson
LM, Chu Y, Iyoha E, Maruthur NM. Diabetes Medications for Adults With Type 2 Diabetes: An
Update. Comparative Effectiveness Review No. 173. (Prepared by the Johns Hopkins University
Evidence-based Practice Center under Contract No. 290-2012-00007-I.) AHRQ Publication No.
16-EHC013-EF. Rockville, MD: Agency for Healthcare Research and Quality; April 2016.
www.effectivehealthcare.ahrq.gov/reports/final.cfm.
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Preface
The Agency for Healthcare Research and Quality (AHRQ), through its Evidence-based
Practice Centers (EPCs), sponsors the development of systematic reviews to assist public- and
private-sector organizations in their efforts to improve the quality of health care in the United
States. These reviews provide comprehensive, science-based information on common, costly
medical conditions, and new health care technologies and strategies.
Systematic reviews are the building blocks underlying evidence-based practice; they focus
attention on the strength and limits of evidence from research studies about the effectiveness and
safety of a clinical intervention. In the context of developing recommendations for practice,
systematic reviews can help clarify whether assertions about the value of the intervention are
based on strong evidence from clinical studies. For more information about AHRQ EPC
systematic reviews, see www.effectivehealthcare.ahrq.gov/reference/purpose.cfm.
AHRQ expects that these systematic reviews will be helpful to health plans, providers,
purchasers, government programs, and the health care system as a whole. Transparency and
stakeholder input are essential to the Effective Health Care Program. Please visit the Web site
(www.effectivehealthcare.ahrq.gov) to see draft research questions and reports or to join an
email list to learn about new program products and opportunities for input.
If you have comments on this systematic review, they may be sent by mail to the Task Order
Officer named below at: Agency for Healthcare Research and Quality, 5600 Fishers Lane,
Rockville, MD 20857, or by email to [email protected].
Richard G. Kronick, Ph.D. Arlene S. Bierman, M.D., M.S.
Director Director
Agency for Healthcare Research and Quality Center for Evidence and Practice
Improvement
Agency for Healthcare Research and Quality
Stephanie Chang, M.D., M.P.H. Elisabeth U. Kato, M.D.
Director Task Order Officer
Evidence-based Practice Center Program Center for Evidence and Practice
Center for Evidence and Practice Improvement Improvement
Agency for Healthcare Research and Quality Agency for Healthcare Research and Quality
Karen C. Lee, M.D., M.P.H.
Task Order Officer
Center for Evidence and Practice
Improvement
Agency for Healthcare Research and Quality
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Acknowledgments
We would like to thank Jessica Gayleard for her help in reviewing articles, Emily Little for
her assistance with the evidence tables, Jeanette Edelstein for copy editing, and Supriya
Janakiraman. We would also like to thank the Technical Expert Panel, Peer Reviewers, Task
Order Officers, and our Associate Editor.
Technical Expert Panel
In designing the study questions and methodology at the outset of this report, the EPC
consulted several technical and content experts. Broad expertise and perspectives were sought.
Divergent and conflicted opinions are common and perceived as healthy scientific discourse that
results in a thoughtful, relevant systematic review. Therefore, in the end, study questions, design,
methodologic approaches, and/or conclusions do not necessarily represent the views of
individual technical and content experts.
Technical Experts must disclose any financial conflicts of interest greater than $10,000 and
any other relevant business or professional conflicts of interest. Because of their unique clinical
or content expertise, individuals with potential conflicts may be retained. The TOO and the EPC
work to balance, manage, or mitigate any potential conflicts of interest identified.
The list of Technical Experts who provided input into this report follows:
John Anderson, M.D. Linda Humphrey, M.D., M.P.H.*
The Frist Clinic Portland Veterans Affairs Medical Center
Nashville, TN Oregon Health & Science University
Portland, OR
Vanita Aroda, M.D.*
MedStar Health Research Institute Leonard Pogach, M.D., M.B.A.*
Hyattsville, MD Veterans Affairs Central Office
Washington, D.C.
Michael Barry, M.D.*
Massachusetts General Hospital Robert Ratner, M.D.
Harvard Medical School American Diabetes Association
Boston, MA Alexandria, VA
Judith Fradkin, M.D.* Christopher Schmid, Ph.D.
National Institute of Diabetes and Digestive Brown University School of Public Health
and Kidney Diseases Providence, RI
Bethesda, MD
*Provided input on Draft Report.
Peer Reviewers
Prior to publication of the final evidence report, EPCs sought input from independent Peer
Reviewers without financial conflicts of interest. However, the conclusions and synthesis of the
scientific literature presented in this report do not necessarily represent the views of individual
reviewers.
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Peer Reviewers must disclose any financial conflicts of interest greater than $10,000 and any
other relevant business or professional conflicts of interest. Because of their unique clinical or
content expertise, individuals with potential nonfinancial conflicts may be retained. The TOO
and the EPC work to balance, manage, or mitigate any potential nonfinancial conflicts of interest
identified.
The list of Peer Reviewers follows:
Jay Desai, Ph.D., M.P.H. Institute for Education and Research
HealthPartners Bloomington, MN
Minneapolis, MN
John Steiner, M.D., M.P.H.
David Graham, M.D., M.P.H. Kaiser Permanente
U.S. Food and Drug Administration Denver, CO
Silver Spring, MD
Patrick O’Connor, M.D., M.A., M.P.H.
HealthPartners Center for Chronic Care
Innovation and HealthPartners
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